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[Relation between serum levels and inotropic effect of digoxin in advanced cardiac failure during long-term
Abstract:
The aim of this study was to determine the relationship of digoxin serum levels to their inotropic effects in advanced cardiac failure during long-term therapy with different dosages. The study was based on the analysis of left ventricular systolic time intervals (STI) measured at 97 follow-up appointments of 20 patients in advanced, stable cardiac failure over an average period of 37 days. The dosage of digoxin was varied at successive consultations so that the serum digoxin levels reached 0.50 ng/ml on at least one occasion. The serum digoxin levels (SD) varied between 0 and 4 ng/ml. Four levels of SD were individualised: A) "control" SD less than 0.25 ng/ml (22 consultations); B) SD: 0.25 to 1 ng/ml (n = 25); C) SD: 1.0 to 2.0 ng/ml (n = 29); D) SD greater than 2 ng/ml (n = 21) including 6 cases with clinical and/or ECG signs of digoxin toxicity. A progressive significant shortening of the electromechanical systolic index (Q-S2 I) was observed up to levels of 2 ng/ml (B and C, -18 ms and -28 ms respectively). The same phenomenon was observed with the ejection time index (ETi) and pre-ejection time index (PETi) (-7 ms and -14 ms; -11 ms and -15 ms respectively) compared to the basal values. At SD greater than 2 ng/ml the reduction remained stable and then started to decrease (positive difference between C and D). These changes were observed in the absence of significant variations of the heart rate. There was a significant linear relationship between the variations of the STI and SD in 15 out of 18 patients (in whom the regression could be calculated, these patients having attended at least 3 appointments). These linear relationships were observed for the Q-S2 i (11-18), the ETi (9-18) and/or PETi (10-18). An unexpected increase in the pre-ejection period was observed in 2 patients. In conclusion, a linear relationship has been shown between SD and inotropic effect which is particularly noticeable at SD levels less than 2 ng/ml. When SD is greater than 2 ng/ml, further increases in SD are associated with smaller variations of the STI. On the other hand, a significant inotropic effect is observed with small doses and SD levels less than 1 ng/ml. This inotropic effect persists unchanged at long-term.